An in vitro system was established for the quantitative chemical transformation of rat epithelial cells (RC-E). These cells can also be transformed by C3H MuLV in conjunction with 12-O-tetradecanoylphorbol-13-acetate (TPA). Transformed cell clones obtained from soft agar generally were virus nonproducers. The purpose of these experiments was to sequence-label TPA-promotable cellular tumor genes and, thus, make possible their isolation by molecular cloning. RC-E cells have also appeared to provide the first system for two-stage carcinogenesis in culture with ethylnitrosourea (ENU) as carcinogen and TPA as tumor-promoter. The observation of cocarcinogenesis of RC-E cells with MuLV and TPA promoted a search for factors homologous to TPA in normal sera. Such a transforming factor was found and purified from normal mouse serum.